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CAML is required for efficient EGF receptor recycling.
David D Tran1, Helen R Russell, Shari L Sutor
1Department of Immunology, Mayo Medical and Graduate Schools, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.
Developmental Cell
|August 16, 2003
Summary
Calcium-modulating cyclophilin ligand (CAML) is essential for early embryonic development and epidermal growth factor (EGF) signaling. CAML deficiency impairs EGF receptor recycling, impacting cell proliferation.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Calcium-modulating cyclophilin ligand (CAML) is a ubiquitous protein involved in TACI receptor signaling in lymphocytes.
- The precise function and mechanism of CAML in cellular processes remain largely unknown.
Purpose of the Study:
- To investigate the role of CAML in mouse development and cellular signaling.
- To elucidate the mechanism by which CAML influences epidermal growth factor receptor (EGFR) signaling.
Main Methods:
- Gene disruption of CAML in mice to create CAML-deficient models.
- Analysis of cellular proliferation, EGF receptor signaling, and receptor trafficking in CAML-deficient cells.
Main Results:
- CAML is indispensable for early embryonic development but not for cell viability.
- CAML-deficient cells exhibit significantly reduced proliferative responses to epidermal growth factor (EGF).
- Defective recycling of internalized EGF receptors (EGFR) to the plasma membrane was observed in CAML-deficient cells, leading to reduced surface EGFR accumulation.
Conclusions:
- CAML plays a critical role in EGFR signaling and is essential for proper EGFR recycling.
- CAML may be involved in mediating long-term proliferative responses to EGF through its role in receptor trafficking.